Beyond intracellular–extracellular divide toward metapopulation infection biology

The binary classification of pathogens as intracellular or extracellular fails to capture the complexity of infections in vivo. We propose the metapopulation infection biology framework, in which infections comprise spatially structured, interacting subpopulations. Drawing on Klebsiella pneumoniae and Cryptococcus neoformans, we discuss how this framework generates testable predictions and informs therapeutic strategies.